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ORIGINAL ARTICLE
Year : 2021  |  Volume : 39  |  Issue : 1  |  Page : 9-15
 

Association between ABO, Rh blood groups, lip and dermatoglyphic patterns, and nonsyndromic oral clefts: A case–control study


1 Regional Medical Centre, Indian Council of Medical Research, Port Blair, Andaman Nicobar Islands; Department of Public Health Dentistry, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India
2 School of Population and Global Health, The University of Western Australia; Telethon Kids Institute, The University of Western Australia, Northern Entrance, Nedlands, Western, Australia
3 Department of Oral and Maxillofacial Pathology, Meenakshi Ammal Dental College and Hospital, Chennai, Tamil Nadu, India
4 Meenakshi Cleft and Craniofacial Centre, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India
5 Cleft Children International, Zurich, Switzerland
6 Department of Public Health Dentistry, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India

Date of Submission17-Jan-2021
Date of Decision15-Feb-2021
Date of Acceptance02-Mar-2021
Date of Web Publication22-Apr-2021

Correspondence Address:
Dr. Mohammed Junaid
School of Population and Global Health, The University of Western Australia, Clifton Street Building, Clifton Street, Nedlands 6009
Australia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jisppd.jisppd_23_21

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   Abstract 


Objective: The objective of the study is to determine the association between nonsyndromic oral clefts (OC) in children and ABO, Rh blood groups, lip, and dermatoglyphic patterns of their unaffected parents. Methods: This case–control study was conducted at a tertiary cleft center in Chennai, India, among 240 individuals comprising 80 units (40 cases and controls, respectively). Each unit (triad) was constituted by a child (0–12 years of age) either born with nonsyndromic OC (cases) or with no diagnosed congenital anomaly (control) and their unaffected parents (mother and father). ABO and Rh blood groups, specific lip print, fingerprint pattern, and palmar asymmetry were recorded for each individual. Strength of association of related factors was assessed by multivariable logistic regression reported as adjusted odds ratios and 95% confidence interval. Results: A1-positive blood group was found to be considerably higher among case mothers (14.39 [1.57–32.27]). A higher odds of OCs were observed among case mothers with whorl lip pattern (1.51 [1.16–3.17]) and radial loop pattern in fingers (1.44 [1.09–2.31]) relative to controls. In addition, palmar asymmetry was distinctively higher among case parents compared to controls (P < 0.01). Conclusion: Findings indicate that A1-positive blood group, higher frequency of whorl lip, and radial loop finger patterns in mothers and higher ulnar loop pattern in fathers and palmar asymmetry in both parents increases odds of occurrence of OC among their offspring. These identifiable traits offer potential scope for better service planning among resource-constrained disadvantaged communities in India.


Keywords: ABO blood group cheiloscopy, dermatoglyphics, lip prints, oral clefts


How to cite this article:
Sivanand N, Junaid M, Sivapathasundaram B, Ramanathan M, Sailer HF, Nijesh J E, Sivasamy S, Chaly PE. Association between ABO, Rh blood groups, lip and dermatoglyphic patterns, and nonsyndromic oral clefts: A case–control study. J Indian Soc Pedod Prev Dent 2021;39:9-15

How to cite this URL:
Sivanand N, Junaid M, Sivapathasundaram B, Ramanathan M, Sailer HF, Nijesh J E, Sivasamy S, Chaly PE. Association between ABO, Rh blood groups, lip and dermatoglyphic patterns, and nonsyndromic oral clefts: A case–control study. J Indian Soc Pedod Prev Dent [serial online] 2021 [cited 2021 Sep 27];39:9-15. Available from: https://www.jisppd.com/text.asp?2021/39/1/9/314358





   Introduction Top


Oral clefts (OCs) are heterogeneous group of craniofacial birth defects arising from an interplay of genetic and environmental factors.[1],[2] Birth prevalence of OC ranges from 1 in 500 to 1 in 2000 live births globally[3] and 0.93 per 1000 live births in India.[4] The pooled prevalence of orofacial clefts in the south Indian region was found to be 1.1 per 1000 total births.[5] Phenotypically, this complexity is presented as unilateral or bilateral cleft lip (CL), isolated cleft palate (CP), or cleft lip and palate (CLP).[2],[6] Most of the reported cleft cases are nonsyndromic (70%–80%) and present as isolated entities with no other apparent cognitive or structural abnormalities.[2],[7]

Environmental factors and their association with OC have been extensively documented. Some of the factors widely studied in this relation include: maternal tobacco exposure, maternal alcohol use, deficiency of folic acid in diet, maternal obesity (and gestational diabetes), teratogenic drugs, and exposure to environmental pollutants.[2] Other important epigenetic factors which are significantly related with OC include parental age, consanguinity, positive family history, and maternal obstetric history.[8],[9],[10] Effect of other factors such as maternal stress and assisted fertilization in the development of OC has also been recently studied.[11],[12] Hence, predicting CL and palate can be considered a major advancement in prevention and will aid to improve the access of genetic services.

Blood group antigens (ABO and Rh) are genetically determined and play a vital role in understanding population genetic studies, inheritance patterns, and susceptibility to disease including OCs.[13] Lip prints are characteristic patterns formed by elevations and depressions in the labial mucosa.[14] They are unique for individuals and do not change during the life of a person.[15] Thus, lip prints may be useful in identification and diagnosis of congenital diseases and anomalies.[3],[15]

Dermatoglyphics is the study of dermal ridge configurations on the fingers, palms, and soles.[16] Phenotypically, excessive asymmetry between dermatoglyphic patterns of both hands signifies an underlying developmental instability resulting from unstable genetic control during embryogenesis which may contribute to the risk of developing OC.[17],[18] Development of primary and secondary palate is completed by the 7th week and 12th week of intrauterine life, respectively. This timing is similar to when epidermal ridges develop in relation to the volar pads (6th week to 13th week of gestation).[18]

These easily identifiable traits could eventually prove useful by helping to tailor risk estimates for the occurrence of nonsyndromic OCs. This would be considered a major advancement as certain phenotypic findings, and blood groups would act as a cue[19] to further analyse individual gestational risk factors which would aid in better service planning, especially among disadvantaged and vulnerable communities. Hence, the aim of the study was to determine the association between of occurrence of nonsyndromic OC in children and ABO, Rh blood groups, lip, and dermatoglyphic patterns of their unaffected parents among an ethnically Dravidian South Indian population.


   Methods Top


This hospital-based case–control study was conducted overall duration of 2 months (September to October 2016). Ethics approval for the study was granted by the Institutional Ethical Committee (MADC/IRB/2016/201). Informed consent was obtained from all participants of the study.

Sampling methodology and eligibility criteria

The study sample was constituted by a total of 240 individuals comprising 80 units (40 cases and control, respectively). Each unit (triad) was constituted by a child (0–12 years of age) either born with nonsyndromic OC (cases) or with no diagnosed congenital anomalies (control) and their unaffected parents (mother and father). Study participants (all new cases) were recruited from a tertiary cleft center and dental hospital situated in Chennai, Tamil Nadu, India. The study participants were ethnically Dravidian residing within a 100 km radius from Chennai city. Sample size was estimated based on results of a pilot study conducted among 30 units in each group (power - 90%, α - 5%) and considering the proportional difference of whorl lip print pattern between case (68%) and control mothers (32%). The case group included infants and children aged up to 12 years, presenting with nonsyndromic CL alone, CP alone, or with CLP with their unaffected parents (40 mothers and 40 fathers). Control group had 40 infants and children up to 12 years of age without any congenital anomaly attending the hospital to treat other dental ailments with their unaffected parents (40 mothers and 40 fathers). The term unaffected parents used in this study refers to parents who were never diagnosed with OC. Individuals with known syndromic OCs, any lesion or inflammatory state of lips, hypersensitivity to lipstick, or previous history of surgery to lips in control group were excluded from the study. Control participants (ethnically Dravidian) were grouped matched according to age (child and parents), religion, and socioeconomic status to minimize any potential confounding.

Data sources/measurement

Lip, finger, and palm prints were recorded by a single calibrated examiner. Before commencing the pilot study, the principal investigator was trained, calibrated, and blinded when rating patients to ensure uniform recording and interpretation of lip prints (kappa statistic = 0.85) and finger and palm prints (kappa statistic = 0.81).

Administration of questionnaire

The customised questionnaire comprised of two sections. First section was used to collect demographic information (age of child and parents, religion, education, occupation, income,[20] and place of residence) from parents, and the second section comprised ten questions (closed ended) pertaining to gestational exposure to risk factors which was recorded through a face-to-face interview with both fathers and mothers of the case and control groups. The questionnaire was initially assessed for validity and was found to have good internal consistency (Cronbach's alpha = 0.78). Type and severity of cleft were recorded in a case record form following Kernahan's classification for OCs.[21]

Blood grouping

Under aseptic conditions, 1 to 2 ml of blood was collected from cases and controls, through venipuncture from the median cubital vein, using a 2 ml disposable syringe and immediately transferred into a 3 ml K3 ethylenediaminetetraacetic acid vacutainer tube by a trained staff nurse. A white porcelain tile method was used for ABO grouping and Rh typing in the present study.[22]

Collection and analysis of lip prints

The lip prints of individuals were obtained using Cellophane method.[14] The impression was subsequently visualized with the use of a magnifying lens. Recorded lip prints were then classified based on K. Suzuki and Tsuchihashi Lip print classification (1970).[15] Determination of patterns depends on numerical superiority of properties of the lines in this study area.

Collection and analysis of finger and palm prints

Rolled prints of each finger and palm were individually recorded from every participant using the Ink Method.[18] After recording, fingerprints were categorized as ulnar loop, radial loop, arch, whorl, or other undefined patterns.[23] Palmar asymmetry was measured by subtracting ATD angles (measured by angle formed between two straight lines between the a and t triradii and the d and t triradii) of the right and left hands, respectively [Figure 1].[18]
Figure 1: Recording ATD angle

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Statistical analysis

Data were analyzed using SPSS software version 20 (IBM Corp. Chicago, IL, USA). Case and control groups were initially compared using Chi-square test and Fisher's exact test for categorical data and independent samples t-test for quantitative data (normally distributed) and Mann–Whitney U-test for ATD angle asymmetry. Significance levels (P value) for these comparisons were corrected to 0.01 using a Bonferroni correction to compensate for multiple pairwise comparisons. Subsequently, multivariable logistic regression analysis was carried out for those variables which demonstrated significant association in the previous analysis. This multivariable regression was conducted as two separate models for mother and father adjusting for selected explanatory variables, and results were reported as adjusted odd's ratios and 95% confidence interval (CI):

  • Model 1 (Mother): OC = A1-positive blood group + Whorl lip pattern + Radial loop pattern + ATD angle asymmetry
  • Model 2 (Father): OC = A1-positive blood group + Ulnar loop pattern + Whorl finger pattern + ATD angle asymmetry.



   Results Top


Of the 60 case units initially screened, 43 satisfied the inclusion criteria. Among the 43 eligible units, 40 consented to participate in the study. Equal numbers of control individuals were selected through group matching after all the case individuals were recruited.

Study participants who reported to the tertiary cleft center and dental hospital predominantly belonged to the upper-lower socioeconomic class. The demographic variables were matched (group matching) during the selection of control individuals to maintain homogeneity [P > 0.05, [Table 1]].
Table 1: Demographic characteristics of the case and control groups

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About half of the children (47.5%) were born with bilateral CLP and two-fifth with left CL (40%) and very few (12.5%) with right CL. Around a third of case children (30%) had A1-positive blood group which was distinctively higher than control children (P = 0.01). Palmar asymmetry reflected by ATD angle asymmetry was higher among case children when compared to their control counterparts [Table 2] and [Table 3].
Table 2: Comparison of frequency of blood groups in case and control groups

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Table 3: Comparison of frequency of lip print, fingerprint patterns, and ATD angle asymmetry in case and control groups

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Mother

About one-fifth of case mothers (20%) had A1-positive blood group and were 14.39 times more likely to have a child born with OC compared to control mothers (14.39 [1.57–32.27]) [Table 2] and [Table 4]. We observed a higher frequency of whorl lip pattern among case mothers (17.5%) which indicated that these mothers had a 51% greater chance for their offspring to develop OC relative to control mothers (1.51 [1.16–3.17]). Radial loop finger pattern found to be higher in case mothers when compared to control mothers (1.44 [1.09–2.31]). However, these mothers had reduced frequency of arches relative to the controls (P < 0.01) [Table 3]. In addition, case mothers presented with greater ATD angle asymmetry when compared to control mothers (37 [9.33–146.65]).
Table 4: Adjusted association for pertinent explanatory variables using multivariable logistic regression

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Father

Frequency of ulnar loop finger pattern was higher among case fathers due to which they carried a 12% higher chance for their children to develop clefting when compared to controls (1.12 [1.01–2.44]). However, greater proportion of whorl pattern (0.60 [0.45–0.81]) was observed among the control fathers (P < 0.01). The ATD angle asymmetry among case fathers was larger than control fathers (5.48 [2.1–14.28]). There was no apparent relationship between the presence of A1-positive blood group among fathers and the occurrence of OC in children in the multivariate model considered [Table 3] and [Table 4].

Gestational risk factors

Among the gestational risk factors considered, nearly two-fifth of case mothers (39%) had a consanguineous marriage when compared to their control counterparts (P = 0.04). In addition, nearly one-fifth of case mothers also reported gestational diseases (19.5%) and a quarter of them had inadequate folic acid intake (25%) during pregnancy. Both these findings were found to be significantly higher when compared to control mothers (P < 0.05, P < 0.01, respectively) [Supplementary Table 1].




   Discussion Top


The present study was first of its kind to estimate odds of occurrence of nonsyndromic OCs using blood groups, lip, and dermatoglyphic patterns among a South Indian population (ethnically Dravidian).

We observed higher frequency of A1-positive blood group among children with OC and their parents when compared to controls. This finding was similar to an earlier study conducted among children alone.[13] Although a positive association was established in our study, the findings must not be viewed independently and must be compared with underlying candidate genes and individual risk factors to enhance quality of evidence of this result.

In our study, higher frequency whorl lip print pattern was observed for case mothers and fathers than controls. Our findings were similar to previous research conducted among Egyptian and other Indian populations;[24] however, previous studies did not compare their findings with a control group. Regardless of methodological or racial differences, the literature and current study demonstrate that whorls on the lower lip are increased in cleft individuals and their parents which might represent a mild form of lower lip pits or fistulae, and if they are indeed more frequent, they may be part of an expanded phenotypic spectrum of nonsyndromic CL or CP.[25]

This study showed no distinct difference toward increased ulnar loop or decreased whorl fingerprints in individuals with OC. These patterns of distribution were interestingly similar to previous studies conducted among other different Asian,[17],[26] American,[27] European,[27] and Latin American[27] population groups. The present study showed higher frequency of radial loops among case mothers that were in contrast to the Iranian population. This observed difference could be a result of ethnic variation.[18]

Our study found a substantive difference in the mean ATD angle asymmetry of children and parents in the case group. This was in line with previous studies conducted among different global ethnic groups.[3],[18],[27],[28] These findings could potentially indicate a degree of developmental instability among children born with OCs.[27],[28] However, we observed wide limits in CIs for this variable in our study, and further studies with a higher sample are required to look into this individual finding among this ethnic group.

Thirty-nine percent of case parents had consanguineous marriage which in line with findings of previous population studies.[8] A significant proportion of the case mothers in the present study reported episodes of illness during pregnancy (19.5%) and insufficient folic acid intake (25%), a finding similar to a study conducted among Saudi women.[29] Pregnant women in India belonging to the lower socioeconomic group are often deprived of adequate nutrition which could be a possible justification of this research finding.[30] Gestational risk factors were presented in this study only to describe their proportion among study participants for improved interpretation of research findings.

The biggest strength of this study was that it was among the first to examine the strength of association of OC and blood groups and lip and finger patterns conducted among one predominant racial and ethnic group in South India. The findings of this study can thus be extrapolated to this population. Our study, however, did not examine patterns of inheritance of blood groups, lip and fingerprint patterns and neither determine any association between phenotypic features and prevalent gestational risk factors as it was not in scope of this project. Going forward, further epidemiological research is required to identify prevalent gestation risk factors and underlying candidate gene in conjunction with these identifiable traits to better understand this congenital condition.


   Conclusion Top


A1-positive blood group, higher frequency of whorl lip and radial loop finger patterns in mothers and higher ulnar loop pattern in fathers, and palmar asymmetry in both parents increase odds of occurrence of OC among their offspring. These identifiable traits offer potential scope for better service planning among resource-constrained disadvantaged communities in India. However, further studies examining this evidence with the underlying genotype and gestational risk factors are essential for effective translation into community practice.

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. We declare that all participants provided informed consent to be part of this study and neither did any investigator in this project have any potential conflicts of interest.

Acknowledgments

The authors are grateful to Cleft Children International for their continued contribution in maintaining the tertiary cleft center. We gratefully acknowledge Dr. J. James Rajesh, Assistant Professor, Department of Forensic Sciences, Sri Venkateswara Medical College Hospital and Research Institute, Puducherry, for his advice and guidance with categorizing fingerprints and Dr. Vaishanvi S for their valuable advice.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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