Worldwide frequency of a common genetic variant of luteinizing hormone: an international collaborative research

Nilsson, Christel; Pettersson, Kim; Millar, Robert P.; Coerver, Katherine A.; Matzuk, Martin M.; Huhtaniemi, Ilpo

doi:10.1016/s0015-0282(97)81430-6

Cited by 84 publications

(58 citation statements)

References 20 publications

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“…Tapanainen et al (61) found lower frequency of this variant in obese PCOS patients suggesting that this LH variant somehow protects obese women from developing symptomatic PCOS and its determination may allow the discrimination between individuals with high and low risks for PCOS, especially in obese women. However, a study in the UK found that occurrence of these mutations was not higher in women with PCOS when compared with healthy women (58). Another study in Singaporean Chinese women confirmed this finding (62).…”

Section: The Luteinizing Hormone (Lh) B-subunit Genementioning

confidence: 92%

“…This first genetic variant is a universally common polymorphism with a prevalence of 18.5%. The highest frequencies found are in northern Europe and the frequency decreases with increasing geographical distance, being lowest in Asia (58). The biological activity of the LH variant in vitro is found to be greater than that of the wild-type LH but the in vivo half-life is shorter than that of normal LH so the bioactivity in vivo remains unclear (59).…”

Section: The Luteinizing Hormone (Lh) B-subunit Genementioning

confidence: 98%

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The genetic basis of polycystic ovary syndrome

Xita

Georgiou

Tsatsoulis

2002

European Journal of Endocrinology

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The disorder is characterized by clinical features of hyperandrogenism, menstrual irregularities and often central obesity and hyperinsulinaemia. PCOS may increase the risk for infertility, type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease and endometrial cancer, emphasizing the need for early diagnosis of the syndrome.The genetic basis of PCOS is unknown. There is a strong familial component but the mode of inheritance is uncertain and several candidate genes have been proposed to contribute to susceptibility. Not only genes involved in steroid hormone biosynthesis have been studied but also genes associated with the regulation of insulin secretion and action since hyperinsulinaemia is a characteristic of PCOS. So far there is evidence that INS VNTR (insulin variable number of tandem repeats) or CYP11a (cholesterol side chain cleavage) genes are associated with this syndrome. PCOS appears, however, to be an oligogenic disorder and more studies are necessary to define the genetic basis.

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Section: The Luteinizing Hormone (Lh) B-subunit Genementioning

confidence: 92%

Section: The Luteinizing Hormone (Lh) B-subunit Genementioning

confidence: 98%

The genetic basis of polycystic ovary syndrome

Xita

Georgiou

Tsatsoulis

2002

European Journal of Endocrinology

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“…The carrier frequency of V‐LH (heterozygotes and homozygotes) in the two study groups (20.9 and 17.6%, respectively. Table 1B) was concordant with the previous report on V‐LH frequency among Estonians determined by the immunoassay‐based isoform detection method (21.3%; Nilsson et al ., 1997). There was no difference in allele and genotype frequencies of V‐LH between idiopathic infertility patients and a population‐based cohort of young men, confirming previous studies (Ramanujam et al ., 2000; Lee et al ., 2003).…”

Section: Discussionmentioning

confidence: 99%

‘Carriers of V‐LH among 1593 Baltic men have significantly higher serum LH’

et al. 2015

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SummaryLuteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V‐LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH β‐subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V‐LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V‐LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V‐LH was detected by genotyping of the underlying DNA polymorphisms using PCR‐RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta‐analysis. No significant difference was detected between young men and infertility patients for the V‐LH allele frequency (11.0 vs. 9.3%, respectively). V‐LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta‐analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V‐LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB ‐211G/T, FSHR Asn680Ser, FSHR ‐29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V‐LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive contribution of V‐LH to the natural variance in male serum LH levels. Its downstream clinical consequences are still to be learned.

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“…10 While several investigators have reported the clinical significance of the variant LH in Japanese patients with reproductive disorders including infertility and/or menstrual disorders, 6 -10,18 Finnish women carrying the variant LH, detected in 28% of the population, were reportedly fertile. 15,19 Thus, evidence concerning the clinical significance of the variant with respect to reproductive disorders has been contradictory, and many unclear areas remain unresolved with respect to the physiological and pathophysiological significance of the variant LH. In this study, it is true that we did not find a statistically significant difference between women with ovulatory disorders and women with normal ovulatory cycles regarding frequency of novel allele of position 984 and 1008 of the variant form of LH.…”

Section: Discussionmentioning

confidence: 99%

Influence of missense mutation and silent mutation of LHβ-subunit gene in Japanese patients with ovulatory disorders

et al. 2003

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The frequency of variant LHb containing two point mutations (T 986 -C and T 1008 -C) and its relationship to reproductive disorders differ widely between ethnic groups. In a Japanese population, variant luteinizing hormone (LH) correlates with ovulatory disorders. Here we examined the relationship between two missense mutations and five silent mutations (C 894 -T, G 1018 -C, C 1036 -A, C 1098 -T and C 1423 -T) in the LHb gene, and ovulatory disorders. We studied 43 patients with ovulatory disorders, 79 patients with normal ovulatory cycles, and 23 healthy men who agreed to join our DNA analysis. PCR-amplified LHb-subunit gene sequences were compared with a base sequence of wild-type LH reported after direct sequencing. The highest frequency (0.945) of novel allele was observed at the position of the C 1036 -A transition. No homozygotes for wild-type LHb (C 1036 ) were identified. The frequency of novel allele in patients with polycystic ovary syndrome, endometriosis, premature ovarian failure and luteal insufficiency was significantly different from that of healthy women. The frequencies of novel alleles (C 894 -T, C 1098 -T and C 1423 -T) in patients with ovulatory disorders were significantly higher than those with normal ovulatory cycles. The mean incidence of point mutation in patients with ovulatory disorders was higher than in those with normal ovulatory cycles. Among patients with variant LH, five silent mutations were identified in 87.5% of patients with ovulatory disorders, whereas only a few silent mutations were identified in patients with normal ovulatory cycles. In a Japanese population, five silent mutations of variant LH could have influenced two missense mutations and/or other unknown missense mutations, causing ovulatory disorders.

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Worldwide frequency of a common genetic variant of luteinizing hormone: an international collaborative research

Cited by 84 publications

References 20 publications

The genetic basis of polycystic ovary syndrome

The genetic basis of polycystic ovary syndrome

‘Carriers of V‐LH among 1593 Baltic men have significantly higher serum LH’

Influence of missense mutation and silent mutation of LHβ-subunit gene in Japanese patients with ovulatory disorders

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